Asymmetric Synthesis and Absolute Configuration of (+)- and (-)-Perhexiline

Racemic perhexiline has been used (or is currently undergoing clinical trials) for the treatment of a variety of cardiovascular disorders. Increasing evidence suggests that the (-)-enantiomer should be used, as opposed to the racemic mixture. Here, we report the first asymmetric synthesis of both enantiomers of perhexiline in high enantiomeric excess and the assignment of their (-)-S/(+)-R absolute stereochemistry by X-ray crystallography.